Motor impairment is present in up to 50% of adults by age 85 and associated with adverse health outcomes. Understanding its neuropathology is essential for efforts to meet this growing public health challenge. The overall goal of Brain and Spinal Cord Microvascular Pathology and Late-Life Motor Impairment is to test the hypothesis that microvascular pathology in the brain and spinal cord contributes to late-life motor impairment. Brain imaging studies suggest that microvascular pathology, as inferred by white matter hyperintensities, is an important factor in late-life motor impairment. We propose to directly investigate specific microvascular pathologies including, arteriolosclerosis, microscopic infarcts and cerebral amyloid angiopathy. These pathologies are not visible via brain imaging and can only be directly studied using histopathologic techniques. Furthermore, to understand late-life motor impairment it is essential to examine both the brain and spinal cord, since damage to either or both can cause motor deficits. Indeed, though microvascular pathology in the spinal cord has been documented, its contribution to late-life motor impairment has not been studied. Furthermore, although microvascular pathology in the brain is recognized as a possible cause of motor impairment, systematic studies of microvascular pathology from motor-related regions of the brain and the spinal cord from the same individuals with clinical data proximate to death are lacking. Compelling preliminary data from post-mortem indices collected in the cognitive-brain regions show that even among older adults without evidence of macroscopic infarcts, microvascular pathology is present in more than 35% of brains and common in the spinal cord. Further, more severe microvascular pathology in the brain is associated with a lower level and more rapid motor decline. Building on these data, we propose to directly examine microvascular pathology in the motor system by taking advantage of the Memory and Aging Project (R01AG17911). This study will donate the clinical and post-mortem specimens they have already collected for the proposed collection of microvascular pathology from the brain and spinal cord from the same individuals. Establishing that microvascular pathology in the brain and spinal cord contributes to progressive late-life motor impairment would fill important gaps in our scientific knowledge and is essential for interventions to alleviate this growing public health challenge. PUBLIC HEALTH RELEVANCE: Motor impairment is present in up to half of all adults by age 85. Demonstrating that microvascular pathology in the brain and spinal cords may underlie late-life motor impairment is essential for efforts to alleviate this growing public health challenge an would greatly expand the role of cerebrovascular pathologies as an important barrier in need of treatment to maintain independence in old age.